Liver cancer is one of the most common malignant tumors in Taiwan, more than 7,000 people died as a result of liver cancer each year. The symptom was not obvious in early stage; the patients feel nothing after having liver cancer for long time. Until the progression of the disease to some degree, it will gradually produce some symptoms such as liver pain, loss of appetite, fatigue, weakness, losing weight etc. At the later stage, patients develop jaundice, ascites, vomiting, coma and other symptoms. Patients with liver cancer often palpable huge tumor on abdominal, however this has come in late, and even metastasis to the lungs and other organs. The overall duration of liver cancer is about two and half years, of which first two years are the early stage without symptoms. Once the symptoms appear, the survival time is only six months. Liver cancer is very difficult to diagnosis. For most of the patients, liver transplantation is their only hope. The method for early diagnosis could save countless lives. Some of the current method of detection of tumor growth is often based on the existence of the blood concentrations of specific markers. For the detection of liver cancer, commonly use α-fetoprotein (AFP) in diagnosing liver cancer. AFP is a normal fetal serum protein synthesized by the liver, yolk sac, and gastrointestinal tract that shares sequence homology with albumin. It is a major component of fetal plasma, reaching a peak concentration of 3 mg/ml at 12 weeks of gestation. AFP can be found in 95% primary liver cancer patients' blood, it is also used as a marker for screening liver cirrhosis and hepatitis. Due to AFP's low specificity, fake positive results are frequently occurs. It is estimated that 6 billion NTD commercial potential exist in Taiwan's market regarding liver caner early diagnosis, and a more gigantic potential exists in foreign market.
The process of N-glycosylation consists of a covalent linkage of a specific oligosaccharide (Glc3Man9GlcNAc2) on a nascent protein. Once the oligosaccharide is transferred, several subsequent steps of maturation will occur along the secretory pathway. N-glycosylation is ubiquitous in eukaryotes. First steps of N-glycosylation are conserved through eukaryotes from yeast to human, which take place in the endoplasmic reticulum. The following and last steps of maturation leading to polymannosylated glycoprotein, which occur in the Golgi apparatus, and are species specific. The function of α-mannosidase is to trim the mammose of the glycoprotein in the process of N-glycosylation. There are many types of α-mannosidase in human. Previous studies revealed that some specific types of mannosidase are related to the formation of cancer, supported with high expression level of mannosidase in particular cancer. Swainsonine (SW), α-mannosidase II inhibitor can efficiently decrease the tumor size in nude mice injected with leukemia cell (MDAY-D2) (Goss, 1995). Deoxymannojirimyci (DMJ), α-mannosidase I inhibitor decreased migration ability of bladder cancer cells (T24) (Przybylo, 2005). DMJ also can induce liver cancer cell (7721) toward apoptosis (Przybylo, 2005). Based on these literatures, the present invention further discover the expression level of four α-mannosidase genes in different stages of liver cancer and their correlation to migration ability. Furthermore, early diagnosis of cancer using α-mannosidase has not been reported previously, and we identified one type of α-mannosidase-MAN1C1 can predict the early stage.